Polysubstance abuse and traumatic brain injury: quantitative magnetic resonance imaging and neuropsychological outcome in older adolescents and young adults.

Few studies have examined the consequences of alcohol and drug abuse on TBI though they commonly co-occur. Both TBI and substance abuse independently result in neuropathological changes in the brain such as ventricular enlargement and cortical atrophy, thus it is reasonable to hypothesize that the combination of the two would result in more significant cerebral damage. In this study, 3 groups of patients--traumatically brain injured (TBI) with substance abuse (N = 19), TBI without substance abuse (N = 19), and substance abuse with no TBI (N = 16)--were compared with normal controls (N = 20) on several quantitative MRI (QMRI) measures. Since TBI most frequently occurs in older adolescents and young men, we examined only male participants between 16 and 30 years of age. Comparing young substance abusers to controls resulted in no QMRI differences. When controlling for head injury severity, the effects of substance abuse in combination with TBI resulted in greater atrophic changes than seen in any other group. TBI and substance abuse patients' neuropsychological test performances also were examined, and no differences were found among patient groups on any measures. These findings have implications for the deleterious interaction of substance abuse combining with TBI to result in greater neuropathological changes that can be detected by QMRI techniques.     

Major depression following traumatic brain injury

BACKGROUND: Major depression is a frequent psychiatric complication among patients with traumatic brain injury (TBI). To our knowledge, however, the clinical correlates of major depression have not been extensively studied. OBJECTIVE: To determine the clinical, neuropsychological, and structural neuroimaging correlates of major depression occurring after TBI. DESIGN: Prospective, case-controlled, surveillance study conducted during the first year after the traumatic episode occurred.Settings University hospital level I trauma center and a specialized rehabilitation unit. METHODS: The study group consisted of 91 patients with TBI. In addition, 27 patients with multiple traumas but without evidence of central nervous system injury constituted the control group. The patients' conditions were evaluated at baseline and at 3, 6, and 12 months after the traumatic episode. Psychiatric diagnosis was made using a structured clinical interview and DSM-IV criteria. Neuropsychological testing and quantitative magnetic resonance imaging were performed at the 3-month follow-up visit. RESULTS: Major depressive disorder was observed in 30 (33%) of 91 patients during the first year after sustaining a TBI. Major depressive disorder was significantly more frequent among patients with TBI than among the controls. Patients with TBI who had major depression were more likely to have a personal history of mood and anxiety disorders than patients who did not have major depression. Patients with major depression exhibited comorbid anxiety (76.7%) and aggressive behavior (56.7%). Patients with major depression had significantly greater impairment in executive functions than their nondepressed counterparts. Major depression was also associated with poorer social functioning at the 6-and 12-month follow-up, as well as significantly reduced left prefrontal gray matter volumes, particularly in the ventrolateral and dorsolateral regions. CONCLUSIONS: Major depression is a frequent complication of TBI that hinders a patient's recovery. It is associated with executive dysfunction, negative affect, and prominent anxiety symptoms. The neuropathological changes produced by TBI may lead to deactivation of lateral and dorsal prefrontal cortices and increased activation of ventral limbic and paralimbic structures including the amygdala.     

Suicidal behavior and mild traumatic brain injury in major depression

Traumatic brain injury (TBI) is associated with psychiatric illness, suicidal ideation, suicide attempts, and completed suicide. We investigated the relationship between mild TBI and other risk factors for suicidal behavior in major depressive episode. We hypothesized that mild TBI would be associated with suicidal behavior at least partly because of shared risk factors that contribute to the diathesis for suicidal acts. Depressed patients (N = 325) presenting for treatment were evaluated for psychopathology, traumatic history, and suicidal behavior. Data were analyzed using Student t -test, chi-square statistic, or Fisher exact test. A backward stepwise logistic regression model (N = 255) examined the relationship between attempter status and variables that differed in the TBI and non-TBI patients. Forty-four percent of all subjects reported mild TBI. Subjects with TBI were more likely to be male, have a history of substance abuse, have cluster B personality disorder, and be more aggressive and hostile compared with subjects without TBI. They were also more likely to be suicide attempters, although their suicidal behavior was not different from that of suicide attempters without TBI. Attempt status was mostly predicted by aggression and hostility, but not the presence of TBI. Of note, for males, a history of TBI increased the likelihood of being a suicide attempter, whereas the risk was elevated for females regardless of TBI history. Our data suggest that suicidal behavior and TBI share antecedent risk factors: hostility and aggression. Future studies may yield confirmation using a prospective design.     

Traumatic brain injury and psychogenic nonepileptic seizures yield worse outcomes

Purpose: To investigate the relationship between traumatic brain injury (TBI) and psychogenic nonepileptic seizures (PNES). We hypothesized that PNES with TBI would be associated with more psychiatric comorbidities and disability than PNES without TBI. Methods: In this cross‐sectional study comparing patients with PNES with TBI to patients with PNES without TBI, medical records from 255 consecutive patients with electroencephalography (EEG)‐confirmed PNES were reviewed to assess variables including demographic, head injury, neurologic, psychiatry, social variables, and quality of life and symptoms scales. Parametric, analysis of covariance (ANCOVA), and logistic regression analyses were performed, to compare psychiatric and function variables between the two study groups while controlling for age and sex. Key Findings: Of the 92 patients with PNES who fulfilled inclusion/exclusion criteria, 41 (44.6%) had a history of TBI. Of the 41 patients with TBI, 30 (73%) met criteria for mild TBI (mTBI). Patients with TBI had more mood disorder diagnoses, were more likely to receive disability, and had lower global functioning than non‐TBI patients with PNES, after adjusting for age and sex. Patients with TBI and PNES had significantly increased odds for having major depression, behavioral impulsivity, posttraumatic stress disorder diagnosis, and a trauma/abuse history. Significance: TBI is a significant risk factor in patients with PNES, being associated with increased psychiatric diagnostic comorbidity, symptoms severity, poorer functioning, and increased disability. This study reveals the importance of identifying and addressing the impact of TBI in patients with seizure disorders. Addressing the sequelae of TBI in PNES may be a target to improve functioning.     

The association of suicide attempts and comorbid depression and substance abuse in psychiatric consultation patients

Substance abuse has been associated with attempted suicide and suicide. Few studies have examined the prevalence and associations of combined depression and substance abuse in suicide attempters. A chart review study of 1136 adult general hospital patients referred for psychiatric consultation between 1995 and 1998 was conducted to assess this further. Among 371 cases with self-harm, 311 (84%) attempted suicide. Suicide attempters were younger and diagnosed more often with comorbid substance abuse than patients without self-harm. Depressive disorders were found in 59% and substance abuse disorders in 46%. Comorbid depression and substance abuse was the most frequent category in suicide attempters, i.e., in 37%. Self-reported suicide intent was associated with increasing age, male gender, and comorbid depression and substance abuse. The suicide rate in suicide attempters was 322 per 100,000 patient-years, and 131 per 100,000 in consultation patients without self-harm. It is concluded that comorbid depression and substance abuse is associated with attempted suicide in psychiatric consultation patients. Suicide attempters should be thoroughly assessed for substance abuse. The increased suicide rate in psychiatric consultation patients with and without suicide attempts warrants further research.     

The influence of traumatic brain injury on treatment outcomes of Concurrent Treatment for PTSD and Substance Use Disorders Using Prolonged Exposure (COPE) in veterans

BackgroundThe co-occurrence of posttraumatic stress disorder (PTSD), substance use disorders (SUD), and traumatic brain injury (TBI) in veterans of Operations Enduring/Iraqi Freedom and New Dawn has received much attention in the literature. Although hypotheses have been presented and disseminated that TBI history will negatively influence treatment response, little data exist to support these claims. The present study investigates the influence of TBI history on response to COPE (Concurrent Treatment of PTSD and SUD Using Prolonged Exposure), a 12-session, integrated psychotherapy designed to address co-occurring PTSD and SUD.MethodParticipants were 51 veterans with current PTSD and SUD enrolled in a clinical trial examining COPE. Assessments of PTSD symptoms, substance use, and depression were collected at baseline and each treatment session. A TBI measure was used to dichotomize veterans into groups with and without a history of TBI (ns = 30 and 21, respectively).ResultsParticipants with and without TBI history demonstrated significant improvements in PTSD and depression symptoms during the course of treatment. However, participants with TBI history experienced less improvement relative to participants without TBI history.ConclusionsThe present findings suggest that, although patients with a TBI history respond to treatment, their response to treatment was less so than that observed in patients without a TBI history. As such, identification, symptom monitoring, and treatment practices may require alteration and further special consideration in individuals with PTSD, SUD and TBI.     

Traumatic brain injury and alcohol/substance abuse: A Bayesian meta-analysis comparing the outcomes of people with and without a history of abuse

Alcohol and substance (drugs and/or alcohol) abuse are major risk factors for traumatic brain injury (TBI); however, it remains unclear whether outcomes differ for those with and without a history of preinjury abuse. A meta-analysis was performed to examine this issue. The PubMed, Embase, and PsycINFO databases were searched for research that compared the neuroradiological, cognitive, or psychological outcomes of adults with and without a documented history of alcohol and/or substance abuse who sustained nonpenetrating TBIs. Data from 22 studies were analyzed using a random-effects model: Hedges’s g effect sizes measured the mean difference in outcomes of individuals with/without a history of preinjury abuse, and Bayes factors assessed the probability that the outcomes differed. Patients with a history of alcohol and/or substance abuse had poorer neuroradiological outcomes, including reduced hippocampal (g = ?0.82) and gray matter volumes (g = ?0.46 to ?0.82), and enlarged cerebral ventricles (g = ?0.73 to ?0.80). There were limited differences in cognitive outcomes: Executive functioning (g = ?0.51) and memory (g = ?0.39 to ?0.43) were moderately affected, but attention and reasoning were not. The findings for fine motor ability, construction, perception, general cognition, and language were inconclusive. Postinjury substance and alcohol use (g = ?0.97 to ?1.07) and emotional functioning (g = ?0.29 to ?0.44) were worse in those with a history of alcohol and/or substance abuse (psychological outcomes). This study highlighted the type and extent of post-TBI differences between persons with and without a history of alcohol or substance abuse, many of which may hamper recovery. However, variation in the criteria for premorbid abuse, limited information regarding the history of abuse, and an absence of preinjury baseline data prevented an assessment of whether the differences predated the TBI, occurred as a result of ongoing alcohol/substance abuse, or reflected the cumulative impact of alcohol/substance abuse and TBI.     

Cognitive and neurobehavioral functioning after mild versus moderate traumatic brain injury in older adults.

This study evaluated the early cognitive and neurobehavioral outcomes of older adults with mild versus moderate traumatic brain injury (TBI). Thirty-five patients who were age 50 years and older and sustained mild or moderate TBI were prospectively recruited from acute care hospitals. Patients were administered cognitive and neurobehavioral measures up to 2 months post-injury. Demographically comparable control participants received the same measures. Patients and controls did not have previous histories of substance abuse, neuropsychiatric disturbance, dementia, or neurologic illness. Moderate TBI patients performed significantly poorer than mild TBI patients and controls on most cognitive measures, whereas the mild patients performed comparably to controls. In contrast, both mild and moderate patients exhibited significantly greater depression and anxiety/somatic concern than controls. The results indicate that the classification of TBI as mild versus moderate is prognostically meaningful as applied to older adults. The findings extend previous investigations in young adults by demonstrating a relatively good cognitive outcome on objective measures, but subjective complaints after a single, uncomplicated mild TBI in older persons.     

Depressed Suicide Attempters with Posttraumatic Stress Disorder

Posttraumatic stress disorder and major depressive disorder are well-established risk factors for suicidal behavior. This study compared depressed suicide attempters with and without comorbid posttraumatic stress disorder with respect to additional diagnoses, global functioning, depressive symptoms, substance abuse, history of traumatic exposure, and suicidal behavior. Adult patients consecutively admitted to a general hospital after a suicide attempt were interviewed and assessed for DSM-IV diagnosis and clinical correlates. Sixty-four patients (71%) were diagnosed with depression; of them, 21 patients (32%) had posttraumatic stress disorder. There were no group differences in social adjustment, depressive symptoms, or suicidal intent. However, the group with comorbid depression and posttraumatic stress disorder had more additional Axis I diagnoses, a higher degree of childhood trauma exposure, and more often reported previous suicide attempts, non-suicidal self-harm, and vengeful suicidal motives. These findings underline the clinical importance of diagnosis and treatment of posttraumatic stress disorder in suicide attempters.     

Factors affecting increased risk for substance use disorders following traumatic brain injury: What we can learn from animal models

Recent studies have helped identify multiple factors affecting increased risk for substance use disorders (SUDs) following traumatic brain injury (TBI). These factors include age at the time of injury, repetitive injury and TBI severity, neurocircuits, neurotransmitter systems, neuroinflammation, and sex differences. This review will address each of these factors by discussing 1) the clinical and preclinical data identifying patient populations at greatest risk for SUDs post-TBI, 2) TBI-related neuropathology in discrete brain regions heavily implicated in SUDs, and 3) the effects of TBI on molecular mechanisms that may drive substance abuse behavior, like dopaminergic and glutamatergic transmission or neuroimmune signaling in mesolimbic regions of the brain. Although these studies have laid the groundwork for identifying factors that affect risk of SUDs post-TBI, additional studies are required. Notably, preclinical models have been shown to recapitulate many of the behavioral, cellular, and neurochemical features of SUDs and TBI. Therefore, these models are well suited for answering important questions that remain in future investigations.     

Prevalence and correlates of traumatic brain injury among delinquent youths

Background Delinquent youth frequently exhibit high‐risk behaviours that can result in serious injury. However, little is known about traumatic brain injuries (TBIs) and their correlates in this population. Aims To examine the period prevalence and correlates of TBIs in delinquent youths. Method Interviews were conducted with 720 (97.3%) residents of 27 Missouri Division of Youth Services rehabilitation facilities between March 1 and May 31, 2003. Participants [mean age (M_age) = 15.5, standard deviation (SD) = 1.2, 87% male] completed measures assessing TBI, substance use, psychiatric symptoms, and antisocial traits/behaviours. TBI was defined as ever having sustained a head injury causing unconsciousness for more than 20 minutes. Results Nearly one‐in‐five youths (18.3%) reported a lifetime TBI. Youths with TBIs were significantly more likely than youths without to be male, have received a psychiatric diagnosis, report an earlier onset of criminal behaviour/substance use and more lifetime substance use problems and past‐year criminal acts, evidence psychiatric symptoms, report lifetime suicidality, be impulsive, fearless, and external in locus of control and criminally victimized in the year preceding incarceration. Male gender and frequency of own criminal victimization were important predictors of TBI in multivariate analyses. Regression analyses adjusted for demographic factors, indicated that youths with TBIs were at significantly elevated risk for current depressive/anxious symptoms, antisocial behaviour, and substance abuse problems. Conclusions TBI is common among delinquent youth and associated with wide ranging psychiatric dysfunction; however, the causal role of TBIs in the pathogenesis of co‐morbid conditions remains unclear. Copyright © 2008 John Wiley & Sons, Ltd.     

Substance abuse and suicidality in schizophrenia: a common risk factor linked to impulsivity

Lifetime substance abuse comorbidity is frequent in schizophrenic patients, but the clinical correlates remain unclear. We have explored the chronological relations between substance abuse and course of schizophrenia, and compared several clinical characteristics and personality dimensions in 50 schizophrenic patients with or without lifetime substance abuse or dependence. Abuse occurred mainly after the first prodromal symptoms and just before the first psychotic episode. Substance-abusing patients were not different from non-substance-abusing patients on the Chapman Physical Anhedonia Scale, PANSS total score, negative subscore or depression item, CGI, treatment response and demographic variables. In contrast, substance-abusing patients had higher scores on the Barratt Impulsivity Scale (total, cognitive and non-planning scores) and had attempted suicide more often. In patients with schizophrenia, as in the general population, substance abuse or dependence appears associated with higher impulsivity and suicidality. High impulsivity could facilitate substance abuse as a maladaptive behavior in response to prodromal symptoms, precipitating the onset of a characterized psychosis.     

Patterns of alcohol use 1 year after traumatic brain injury: a population-based, epidemiological study.

This study delineated patterns of alcohol use 1 year after traumatic brain injury (TBI) in a large, population-based, epidemiological, nonclinical sample, and identified predictors of heavy alcohol use in these individuals. Participants were 1,606 adults identified by review of a South Carolina statewide hospital discharge data set, on the basis of satisfying the Centers for Disease Control case definition of TBI, and were interviewed by telephone 1 year after TBI-related discharge. Alcohol use in the month prior to interview was classified according to categories from the Quantity-Frequency-Variability Index; heavy drinking was defined as nearly daily use with > or = 5 drinks at least occasionally, or at least three occasions with > or = 5 drinks. A polychotomous logistic regression with 3 response levels (heavy, moderate, and abstinent/infrequent/light drinking) was used to identify predictors of heavy drinking. Heavy drinking in the month prior to interview was reported by 15.4% of participants, while 14.3% reported moderate drinking and 70.3% reported abstinence or light/infrequent drinking. Risk factors for heavy drinking included male gender, younger age, history of substance abuse prior to TBI, diagnosis of depression since TBI, fair/moderate mental health, and better physical functioning. There was no association between drinking patterns and TBI severity.     

Cognitive impairment associated with major depression following mild and moderate traumatic brain injury

Traumatic brain injury (TBI) and major depression are neuropsychiatric conditions that have been associated with cognitive dysfunction. The aim of this study was to explore the relationship between major depression and cognitive impairment following mild and moderate TBI. Seventy-four TBI patients were assessed for the presence of major depression using the Structured Clinical Interview for the DSM-IV and completed a neurocognitive assessment battery. Subjects with major depression (28.4%), compared to those without, were found to have significantly lower scores on measures of working memory, processing speed, verbal memory and executive function. Potential mechanisms and implications for treatment are discussed.     

Alcohol misuse and mood disorders following traumatic brain injury

CONTEXT: Alcohol abuse and/or dependence (AA/D) and mood disturbance are co-occurring conditions among patients who have had a traumatic brain injury (TBI). However, the relationship between these disorders has not been extensively studied. OBJECTIVE: To examine the relationship of AA/D and post-TBI mood disorders and the effect of these conditions on psychosocial outcome. DESIGN: Prospective, case-control surveillance study conducted during the first year following trauma.Settings University hospital level I trauma centers and specialized rehabilitation units.Patients One hundred fifty-eight TBI patients with closed head injury with and without a history of AA/D. METHODS: We prospectively compared psychiatric, neuropsychological, and psychosocial outcomes among the patients, who were evaluated at baseline and at 3, 6, and 12 months after trauma. Psychiatric diagnosis was made using a structured clinical interview and DSM-IV criteria. Neuropsychological testing results and quantitative magnetic resonance images were obtained at the 3-month follow-up. RESULTS: A history of AA/D was significantly more frequent among patients who developed mood disorders during the first year following TBI. There was also a significantly higher frequency of mood disorders among patients with alcohol abuse relapse. Patients with a history of AA/D had significantly reduced frontal gray matter volumes than did patients without a history of alcohol abuse. In addition, patients who resumed alcohol abuse had decreased medial frontal gray matter volumes and impaired performance in executive tasks. Both AA/D and mood disorders following TBI were associated with a poor vocational outcome. CONCLUSIONS: Previous alcohol abuse increases the risk of developing mood disorders after TBI, and emotional disturbance, in turn, increases the risk of alcohol abuse relapse. Alcohol's neurotoxic effects and TBI likely interact to produce greater disruption of the neural circuits that modulate reward, mood, and executive function. Patients with a history of AA/D who also developed mood disorders following TBI had major difficulties resuming a productive life.     

Antisocial personality disorder in Turkish substance dependent patients and its relationship with anxiety, depression and a history of childhood abuse

The prevalence of antisocial personality disorder (ASPD) in treatment-seeking Turkish substance dependent patients and the relationship of ASPD with clinical characteristics were studied. Participants were 132 inpatients with substance dependence according to the Structured Clinical Interview for DSM-IV (SCID-I), Turkish version. The clinician applied a semi-structured socio-demographic form, SCID-I, SCID-II, Childhood Abuse and Neglect Questionnaire (CANQ), Michigan Alcoholism Screening Test (MAST), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Among the 132 substance dependent patients, 31 (23.5%) had ASPD diagnosis and 56 (42.4%) had no personality disorder or personality traits. Rate of childhood physical abuse, childhood verbal abuse, childhood neglect, suicide attempt history, self-destructive behavior and lifetime major depression were higher among patients with ASPD. Also mean scores of BDI, BAI and MAST were higher among patients with ASPD. The high rate of ASPD found among Turkish substance dependent patients suggests that special attention must be paid to identify ASPD in this group. Findings in this study showed that there is an association between ASPD and childhood abuse, lifetime major depression and severity of substance use.     

Cytochrome c, a biomarker of apoptosis, is increased in cerebrospinal fluid from infants with inflicted brain injury from child abuse.

Previous studies suggest that delayed neuronal death occurs in patients with inflicted traumatic brain injury (TBI) from child abuse. It is unknown whether the mode of this delayed neuronal death represents apoptosis or necrosis, a distinction that carries therapeutic ramifications. Cytochrome c, an electron transport chain component, can be released from mitochondria under conditions of cellular stress, whereupon it can initiate and serve as a biomarker of apoptosis. To resolve this issue, cytochrome c concentration was determined in 167 ventricular cerebrospinal fluid (CSF) samples from 67 infants and children with TBI (including 15 patients diagnosed with child abuse) by ELISA. Controls included lumbar CSF from 19 infants and children without trauma or meningitis. A multivariate model adjusted for multiple within-subject observations was used to identify clinical variables associated with CSF cytochrome c. Other apoptosis-related proteins were also examined in a subset of TBI patients. Increased CSF cytochrome c was independently associated with inflicted TBI (P=0.0001) and female gender (P=0.04), but not age, Glasgow coma scale score, or survival. Other apoptosis-related proteins including Fas and caspase-1 were increased in CSF after TBI, but did not independently discriminate between accidental and inflicted TBI. These data suggest that apoptosis, as detected by the presence of cytochrome c in CSF, is uniquely prominent among the subset of TBI patients diagnosed with child abuse. The degree of apoptosis after TBI also appears to be gender-dependent. Development of strategies targeting apoptosis after TBI, particularly in victims of child abuse and in girls, appears justified.     

颅脑外伤患者的抑郁症状及相关因素研究

目的：研究颅脑外伤后患者的抑郁症状及相关因素,方法：对63例急性期颅脑外伤患者,采用标准化测评工具,包括《格拉斯哥昏迷评分（GCS）》,《汉密顿抑郁量表（HRSD）》,《社会支持评定量表》,《日常生活能力量表》及自制颅脑外伤患者人口学与相关因素调查表等。逐例进行现场临床测评,汇总资料进行整理,分析,所有统计分析均使用SAS软件包完成。结果。颅脑外伤患者抑郁症状的发生率为42．86％,其中,重度,中度,轻度抑郁的发生率辚3．17％,7．93％,31．74％,不同外伤类型,年龄,性格,外伤原因及患者对外伤持不同态度的颅脑外伤患者抑郁症状的发生率存在显著性差异,主要影响颅脑外伤后抑郁症状的因素有外伤程度,性格,社会支持,病理征及年龄。结论：提示除了外伤的生物学影响外,抑郁的发生与患者个体的生理心理特点和社会环境因素密切相关。     

Criminality in men with major mental disorder with and without comorbid substance abuse

Violent and criminal behavior in the mentally ill remains an issue of major importance and in this context the role of comorbid substance abuse must be addressed. Data on criminal behavior in 282 men with schizophrenia and 261 men with affective disorder were studied. Samples of patients with and without additional substance abuse were compared. Also, non-abusing patients from both diagnostic groups were compared with matched controls from the general population. Substance abuse was found in half of all men in both groups of major mental disorders, and substance abusers had twice as high a probability of having a criminal record. However, compared with the matched sample from the general population, violent criminality was increased in schizophrenic patients without comorbid substance abuse, and patients with affective disorders without substance abuse had a higher probability of committing crimes against property. Men with major mental disorder have an increased probability of becoming criminal even when there is no comorbid substance abuse.     

Histories of substance abuse in patients with postpsychotic depressions

Forty-six schizophrenic or schizoaffective patients with operationally defined episodes of postpsychotic depression were assessed for previous histories of substance abuse. Thirty-five percent had histories of previous cannabis (marijuana) abuse. Additionally, 13% had also abused cocaine, 13% amphetamines, 11% hallucinogens, 4% sedatives, and 2% opiates. Patients with histories of substance abuse were younger and showed higher index ratings on a subscale of endogenous depressive features. These findings are considered in the context of a possible self-medication hypothesis of substance abuse. A history of substance abuse did not appear to be a contraindication to a therapeutic trial of adjunctive imipramine (Ciba Geigy Corp., Summit, NJ) for postpsychotic depression.